Orphan Drug Act of 1983

Background

Emergence of orphan diseases

In response to incidents such as difficulties with thalidomide the Kefauver-Harris Amendment was passed in 1962 as an amendment to the Federal Food, Drug, and Cosmetic Act. Kefauver-Harris required that all drugs approved for sale be proven safe and effective via rigorous scientific studies. While this legislation improved drug safety, it also dramatically increased the costs associated with developing new medicines. Pharmaceutical companies responded by focusing on developing treatments for common diseases in order to maximize the possibility of recouping research and development costs and generating significant profits. As a result, rare diseases were largely ignored due to poor economic potential and were thus said to be "orphaned." The gap between drugs for common versus rare diseases eventually widened to the point where few or no treatments were available for some rare conditions such as Crohn's disease, Hansen's disease, etc.{{cite journal

Key issues

Main article: Orphan drug

Orphan drugs generally follow the same regulatory development path as any other pharmaceutical product, in which testing focuses on pharmacokinetics and pharmacodynamics, dosing, stability, safety and efficacy. However, some statistical burdens are lessened in an effort to maintain development momentum. For example, orphan drug regulations generally acknowledge the fact that it may not be possible to test 1,000 patients in a phase III clinical trial, as fewer than that number may be affected by the disease in question.

Since the market for any drug with such a limited application scope would, by definition, be small and thus largely unprofitable, government intervention is often required to motivate a manufacturer to address the need for an orphan drug.

The intervention by government on behalf of orphan drug development can take a variety of forms:

• Tax incentives.
• Enhanced patent protection and marketing rights.
• Clinical research subsidies.
• Creating a government-run enterprise to engage in research and development.

Legislation

The plight of patients with rare diseases became an important political issue in the late 1970s and early 1980s. The US government was subject to pressure from activist groups such as NORD and many others.

The chief sponsor of the bill (H.R. 5238) was Henry Waxman (sometimes referred to as the author of the Act),{{Cite news

Market exclusivity is particularly appealing to pharmaceutical firms as an incentive to pursue orphan drug development. The seven-year market exclusivity period differs from traditional patent law in that it does not begin until the drug is granted FDA approval and is independent of the drug's current patent status. Furthermore, if a market competitor wishes to introduce a drug for the same indication, the onus is on the competitor to prove that their drug is therapeutically superior (e.g. increased efficacy, less toxicity, etc.) when compared to the present drug indicated for the rare disease of interest. This incentive creates an attractive monopolistic market for companies interested in developing a product for any given rare disease.

Television historian and Allmovie contributor Hal Erickson credits two episodes of the television series Quincy, M.E. for helping the ODA pass in the USA: "Seldom Silent, Never Heard" (1981) and "Give Me Your Weak" (1982).{{cite web

Effectiveness

Drug companies nearly universally believe the ODA to be a success. Before Congress enacted the ODA in 1983 only 38 drugs were approved in the USA specifically to treat orphan diseases. In the US, from January 1983 to June 2004, a total of 1,129 different orphan drug designations have been granted by the Office of Orphan Products Development (OOPD) and 249 orphan drugs have received marketing authorization. In contrast, the decade prior to 1983 saw fewer than ten such products come to market. From the passage of the ODA in 1983 until May 2010, the FDA approved 353 orphan drugs and granted orphan designations to 2,116 compounds. As of 2010, 200 of the roughly 7,000 officially designated orphan diseases have become treatable. In 2010, drugmaker Pfizer established a division to focus specifically on the development of orphan drugs as other large pharmaceutical companies focused greater efforts on the orphan drug research.

Some critics have questioned whether orphan drug legislation was the real cause of this increase (claiming that many of the new drugs were for disorders that were already being researched anyway, and would have had drugs developed regardless of the legislation), and whether the ODA has really stimulated the production of truly non-profitable drugs; the act also received some criticism for allowing some pharmaceutical companies to make a large profit off of drugs that have a small market but still sell for a high price. While orphan drug status is given to drugs with "no reasonable expectation" of profitability, some orphan drugs have gone on to net large profits and/or receive widespread use. The topic of profit in the aftermath of the ODA was addressed in November 2013 in the Seattle Times where the following quote appeared:

Provigil was an orphan drug and went on to be a blockbuster.

Regulatory harmonization

In an effort to reduce the burden on manufacturers applying for orphan drug status, the FDA and the European Medicines Agency (EMA) agreed in late 2007 to utilize a common application process for both agencies. However, the two agencies will continue to maintain separate approval processes.{{cite news

References

References

1. (4 January 1983). "Orphan Drug Act of 1983". US Food and Drug Administration.
2. Parisse-Brassens, Jerome. (June 2007). "Abbey Meyers, President of NORD, announces her retirement (July 07)". [[European Organization for Rare Disorders]].
3. (March 2018). "Millions Around World to Observe Rare Disease Day". [[PR Newswire]] }}{{dead link.
4. Henkel, John. (1999). "Orphan Drug Law Matures into Medical Mainstay". [[U.S. Food and Drug Administration]].
5. Hadjivasiliou, Andreas. (October 2014). "Orphan Drug Report 2014". EvaluatePharma.
6. (13 November 2018). "Episode 329: Orphan Drugs".
7. (March 2023)
8. [https://news.google.com/newspapers?id=M94qAAAAIBAJ&sjid=GYMDAAAAIBAJ&pg=4422%2C3068432 Klugman winds up his 'Quincy' career], The Deseret News - Mar 23, 1983
9. Rich Daly. (5 September 2002). "House Offers Incentives For Development of 'Orphan' Drugs". Congressional Quarterly Daily Monitor.
10. Armstrong, Walter. (May 2010). "Pharma's Orphans". Pharmaceutical Executive.
11. Grogan, Kevin. (15 June 2010). "Bookmark and Share Pfizer creates orphan disease research division". Pharma Times.
12. Conway, Benjamin. (1 March 2010). "Big Pharma Reassesses Orphan Drug Sector". Wall Street BioBeat.
13. Schulte, Fred. (18 December 2007). "Drug earning millions despite 'orphan' label". Baltimore Sun.
14. (February 21, 2012). "The prevalence and cost of unapproved uses of top-selling orphan drugs". PLOS ONE.